Stabilized formulation comprising omega-3 fatty acids and use of the fatty acids for skin care and/or wound care

ABSTRACT

A stabilized formulation for skin care, wound care and/or other tissue healing applications and methods for making the same is described. The stabilized formulation stabilizes omega-3 polyunsaturated fatty acids and is constituted of the omega-3 polyunsaturated fatty acids in combination with tocopherol (Vitamin E), ascorbic acid (Vitamin C), herb extract, and a fat-soluble antioxidant. Methods for making and using the stabilized formulation are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.13/114,106 (now allowed as U.S. Pat. No. 8,568,795), filed 24 May 2011.U.S. patent application Ser. No. 13/114,106 claims the benefit of andpriority to U.S. Provisional Application No. 61/348,357, filed on 26 May2010. The entireties of the foregoing applications are herebyincorporated herein by reference.

FIELD

This invention relates to a formulation for stabilizing omega-3polyunsaturated fatty acids. The formulation comprises the omega-3polyunsaturated fatty acids in combination with tocopherol (Vitamin E),ascorbic acid (Vitamin C), herb extract, and a fat-soluble antioxidant.This stabilized formulation retards omega-3 polyunsaturated fatty acidoxidation and degradation so that the fatty acids can be used incosmetic and pharmaceutical creams for treatment of various skinconditions and wounds.

BACKGROUND

The outermost layer of the skin consists of 15 to 20 cell layers ofliving cells that die and dry out to build the corneal layer of theskin. Between the dried cells is the intercellular substance, which isrich in epidermal lipids to keep the structure intact and watertight.The corneal layers of the skin are prone to lose the intercellularlipids. The result is that the corneal layer loses volume and no longerprotects the living cells inside. This may lead to inflammation,callosities and fissures. Fatty acids can be applied to the skin toincrease the amount of intercellular lipids in the skin.

Omega-3 fatty acids (also known as .omega.-3 fatty acids or n-3 fattyacids) are a family of unsaturated fatty acids that have a finalcarbon-carbon double bond in the n-3 position (i.e. the third bond fromthe methyl end of the fatty acid). Oils derived from marine sourcescontain high proportions of the healthy polyunsaturated omega-3 fattyacids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), ascompared to alpha-linolenic acid (ALA) which needs to be converted bythe body to EPA and DHA to be useful. EPA and DHA derived from fish oilshave been shown to play an important structural role and influencefluidity in cell membranes. Topically applied plant derived fatty acids,in contrast, are less usable by the skin. However, marine derived fattyacids tend to be unstable and oxidize quickly resulting in bad smell.Thus, there is a need for compositions which increase the stability ofmarine derived fatty acids. The present invention satisfies this need.

SUMMARY

Oils derived from marine sources, such as fish oils, are particularlyhigh in the polyunsaturated omega-3 fatty acids eicosapentaenoic acid(EPA) and docosahexaenoic acid (DHA), which are helpful for treatingvarious skin conditions and wounds. However, marine oils are moredifficult to stabilize than oils from other sources, such as plant oils.The stabilized formulations described herein, comprising tocopherol(Vitamin E), ascorbic acid (Vitamin C), herb extract, and a fat-solubleantioxidant, inhibit degradation and oxidation of omega-3polyunsaturated fatty acids from marine oils. This invention alsorelates to methods of making and using the stabilized formulations.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a chromatograph of a marine based oil that can be used inthe compositions and methods of the present application.

FIG. 2 shows the fatty acid compositions for the peaks in thechromatograph shown in FIG. 1; EPA (peak #20) and DHA (peak #24) arevolume based 19.6% and 12.6%, respectively.

DESCRIPTION

Marine derived omega-3 polyunsaturated fatty acids are very difficult tostabilize, and are easily oxidized and damaged. They are thereforedifficult to use in cosmetics or pharmaceuticals that should have ashelf life of more than 6 months. Commercial fish oils, for example, areusually processed with the addition of natural antioxidants, such astocopherols. The present inventors have unexpectedly found that theformulation described herein is useful for further inhibiting theoxidation of polyunsaturated oils beyond what is provided by theantioxidants that are added at the time the oil is initially processed.Oxidation studies were conducted and it was found that the presentcompositions provide additional unexpectedly significant protection ofpolyunsaturated oils from degradation and/or oxidation.

Described herein is a formulation for stabilizing omega-3polyunsaturated fatty acids, comprising omega-3 polyunsaturated fattyacids in combination with tocopherol (Vitamin E), ascorbic acid (VitaminC), herb extract, and a fat-soluble antioxidant. This stabilizedformulation can slow the oxidation process down to an acceptable levelfor use in cosmetic and pharmaceutical creams. In some embodiments,oxidation of the omega-3 polyunsaturated fatty acids is slowed for atleast 12 months, such as for at least 24, 23, 22, 21, 20, 19, 18, 17,16, 15, 14, or 13 months. Oxidation tests are known in the art.Stability of the omega-3 polyunsaturated fatty acids can be evaluatedby, for example, odor or smell tests, or more quantitatively by peroxidetests with titration.

Suitable tocopherols include alpha-, beta-, delta-, and gamma-tocopheroland alpha-, beta-, delta- and gammatocotrienol. In certain embodiments,the tocopherol is alpha-tocopherol. The tocopherols can be used in thestabilized formulation in an amount of from about 0.005 to about 0.5% byweight of the total composition, such as about 0.01, 0.02, 0.03, 0.04,0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, or 0.4% by weight of thecomposition.

Suitable herb extracts include extracts of rosemary, oregano, basil,marjoram, thyme (timian), black pepper, caraway, cardamom, chives,calorifico, coriander, cumin, dill, garlic, ginger, laurel, nutmeg,onion, parsley, sage, savory and tarragon. In certain embodiments theherb extract is an extract of rosemary. Rosemary (RosmarinusOfficinalis) is an aromatic herb and known stabilization additive (see,e.g., Mariutti et al. (2008) Free Radical Scavenging Activity ofEthanolic Extracts from Herbs and Spices Commercialized in Brazil,Brazilian Archives of Biology and Technology 53:1225-1232 and Wojdylo etal. (2007) Antioxidant Activity and Phenolic Compounds in 32 SelectedHerbs, Food chemistry 105:940-949).

“Herb extract” is a generic term describing a number of differentchemical compositions that may contain several different activecomponents. Among the common components that are found in, e.g.,rosemary extract are carnosol, carnosic acid, methoxy carnosic acid,rosmarinic acid, rosmanol and rosmaridiphenol, in different proportionsdepending on the individual extract. Rosemary extract may also containquinine and several additional beneficial substances with antioxidantproperties, like eucalyptol, borneol, pinene, and camphor.

The herb extract can be, for example, an alcohol or aqueous abstract,and methods of making herb extracts are known in the art. In addition,numerous herb extracts are available commercially. Examples includeRosemary Leaf Extract available from MakingCosmetics Inc. (Renton,Wash., USA) and GUARDIAN™ Rosemary Extract available from Earth SuppliedProducts LLC (Naples, Fla.). The Rosemary Leaf Extract fromMakingCosmetics Inc., used in the examples described below, is extractedin glycerin and water.

The term “rosemary extract” as used herein encompasses not only arosemary extract per se, but also a composition to which the individualactive components, such as are noted above, are added to the compositionindividually, or in individual combinations, from synthetic or naturalsources, either from rosemary or from starting material other thanrosemary, in amounts equivalent to those found in the rosemary extract.

The herb extract can be used in the stabilized formulation in an amountof from about 0.05 to about 5% by weight of the total composition, suchabout 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, or 4% byweight of the composition.

Suitable fat-soluble antioxidants are available on the market andinclude synthetic antioxidants such as BHT (butylalted hydroxytoluene),BHA (butylated hydroxyanisole) and TBHQ (tertiary butyl hydroquinone).BHT, for example, is a widely used food preservative that neutralizesfree radicals and prevents auto-oxidation of organic material. Thefat-soluble antioxidant can be used in the stabilized formulation in anamount of from about 0.01 to about 10% by weight of the totalcomposition, such as about 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.25, 0.3,0.4, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, or 9% by weight of the composition.

The omega-3 polyunsaturated fatty acids can be derived from one or moreoil sources including marine oils (e.g. fish, krill, marine algae, andcalamari oils), seed oils, plant oils, and algal oils, comprising atleast one fatty acid selected from the group consisting of DHA and EPA.The term “fatty acid” as used herein refers to a fatty acid that may bein free form, a monoglyceride, a diglyceride, a triglyceride, an esteror solvate thereof, a pharmaceutically acceptable salt thereof, orcombinations thereof. The omega-3 polyunsaturated fatty acids aregenerally provided in a marine oil, for example a fish oil. Fish oils,particularly fish oils from cold water oily fish, are particularly richin DHA and EPA. Examples of fish high in omega-3 oil include salmon,pilchards, tuna, herring, cod, anchovies, sardines, mackerel, sablefish, smelts, whitefish, hoki fish, and some varieties of trout. Incertain embodiments the omega-3 polyunsaturated fatty acids are from oilwhich is pharmaceutically acceptable according to Pharmacopeia standards(i.e. pharmaceutical grade oils). Such oils includecommercially-available marine omega oils such as Omega-3 Fish Oil (LysiLtd., Iceland). Omega-3 Fish Oil from Lysi Ltd. was used in the examplesdescribed below. Marine oils can be used in the stabilized formulationin an amount of from about 0.001-99% by weight of the total composition,such as from about 0.01-99, 0.1-99, 1-99, 10-99, 20-99, 30-99, 40-99,50-99, 60-99, 70-99, or 80-99% by weight of the composition.

In certain embodiments, the marine oil itself comprises from about0.1-60% by weight of the marine oil, such as from about 5-60, 10-40, or10-20% by weight of DHA and/or from about 0.1-60, such as from about5-60, 10-40, or 10-20% by weight of EPA. The marine oil can alsocomprise other fatty acid or non-fatty acid components naturally foundin fish or added to commercial marine oils.

Tests and trials have shown that formulations having as little as 0.15%(w/w) of EPA and DHA have substantial effects on the process of healingdamaged skin (data not shown).

In certain embodiments, the omega-3 polyunsaturated fatty acids can befrom particulates of the scaffold material prepared in accordance withSigurjonsson et al., U.S. patent application Ser. No. 12/899,123, filedon Oct. 6, 2010, rather than from fish oil. The particulates areprepared by grinding the scaffold material to a grain size of about 0.01to about 5 mm in diameter, such as about 0.02, 0.03, 0.04, 0.05, 0.06,0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, or 4mm in diameter. Alternatively, the scaffold material described in U.S.patent application Ser. No. 12/899,123 can be dissolved (e.g. partiallyor completely gelatinized in an acidic or basic solution) rather thanparticulated.

The stabilized formulations described above, comprising omega-3polyunsaturated fatty acids, tocopherol (Vitamin E), ascorbic acid(Vitamin C), herb extract, and a fat-soluble antioxidant, are useful fortreating various dermatological conditions, including dry skin, atopicdermatitis, allergic contact dermatitis, and radiation dermatitis. Theformulations may also be useful for treating first and second degreewounds, sunburns, superficial injuries, abrasions, cuts, surgicalwounds, pressure ulcers, venous stasis ulcers, ulcers caused by mixedetiologies, diabetic ulcers, donor sites, and grafts. The stabilizedformulations are suitable for treating any type of dry skin wherecallosity formation is a problem. The diabetic foot, for example, isparticularly susceptible to the loss of intercellular lipids in theskin.

The stabilized formulations can also be used in compositions comprisingthe stabilized formulations in combination with one or more additionaltherapeutically active compounds (i.e. active agents), such asexfoliates or other agents that may increase the permeability of theskin so that the polyunsaturated fatty acids can enter the skin moreeasily (e.g. alpha hydroxyl acids (AHAs) such as glycolic acid lacticacid), water retaining chemicals and moisturizers (e.g. urea, propyleneglycol (PPG)), and polyacrylic acid. Other suitable additionaltherapeutically active compounds include antiseptics, antimicrobialagents, antivirals, antifungals, antiparasitics, anti-inflammatoryagents, antioxidants, drugs, proteins, and peptides.

In certain embodiments the compositions comprise (in addition to thestabilized formulation) one or more AHAs. AHAs may improve thepenetration of the polyunsaturated fatty acids into the skin; improvethe penetration of other ingredients of the compositions (e.g. urea)into the skin; and work in concert with the components of the stabilizedformulation to enhance the stability of the polyunsaturated fatty acids.

In certain embodiments the compositions comprise AHA and urea, and canfurther comprise one or more of polypropylene glycol, an aqueouscarrier, paraffin liquid, petrolatum, lanolin alcohol, cetearyl alcohol,and fragrance.

In addition, one or more pharmaceutically and/or cosmetically acceptablediluents, excipients or carriers can be added. For example, thecomposition may comprise substances which assist in its application orstorage stability, such as, e.g., stabilizers, preservatives,pharmaceutical adjuvants, water, buffer substances, thickening agents,emulsifiers, and the like. The techniques of preparing pharmaceuticalcompositions are generally well known in the art as exemplified byRemington's Pharmaceutical Sciences, 16^(th) Ed. Mack PublishingCompany, 1980. Moreover, for human administration, preparations may needto meet sterility, pyrogenicity, and general safety and puritystandards, e.g. as required by the FDA Office of Biological Standards.

In certain embodiments, the compositions are topically administered.“Topical” administration means local, external administration to skinand/or to a wound. The composition may be topically administereddirectly to all or to part of the area of skin or the wound in need oftreatment, or peripherally to the skin area or the wound.

For topical administration, for example, the compositions can beformulated as a gel, ointment, cream, balm, or lotion. Topicaladministration can also be accomplished with a liquid spray, an aerosol,or via iontophoresis, or through the use of liposomes, microbubblesand/or microcapsules. Gels, ointments and creams may be formulated, forexample, with an aqueous or oily base with the addition of suitablethickening (e.g., wax, beeswax, PEG 4000, PEG 600, hard paraffin) and/orgelling agents (e.g., hydroxypropyl cellulose). Lotions may beformulated with an aqueous or oily base and can also generally containone or more emulsifying agents (e.g., wool wax alcohol, fatty acidglycol esters), stabilizing agents (e.g., polyoxyethylene sorbitanmonolaurate, carboxy methyl cellulose), dispersing agents (e.g., sodiumoleate, propylene glycol), suspending agents (e.g., methyl cellulose,chitosan, accacia, carboxymethyl cellulose, tragacanth, pectin),thickening agents, and/or coloring agents (e.g., dyes, lackes). Otherconventional pharmaceutical excipients for topical application includepluronic gels, polaxamer gels, hydrogels containing cellulosederivatives, including hydroxyethyl cellulose, hydroxymethyl cellulose,carboxymethyl cellulose, hydroxypropylmethyl cellulose and mixturesthereof; and hydrogels containing polyacrylic acid (carbopols). Suitablecarriers also include creams/ointments conventionally used for topicalpharmaceutical preparations, e.g., creams based on cetomacrogolemulsifying ointment. The above carriers may include alginate (as athickener or stimulant), preservatives such as benzyl alcohol, buffersto control pH such as disodium hydrogen phosphate/sodium dihydrogenphosphate, agents to adjust osmolarity such as sodium chloride, andstabilizers such as EDTA. In certain embodiments, the presentcomposition comprises wax in an amount ranging from 1-50% by weightbased on 100% by weight of the total composition, such as 5-40%, 10-30%,15-25%, or 20% by weight based on 100% by weight of the totalcomposition.

The stabilized formulation can be applied directly to the skin or woundas a gel, ointment, liquid, cream, or the like as described above.Alternatively, the stabilized formulation is administered in the form ofa wound dressing. As used herein, the terms “wound dressing” and“dressing” refer broadly to any substrate when prepared for, and appliedto, a wound for protection, absorbance, drainage, improvement of cellenvironment, etc., and may include any one of the numerous types ofsubstrates and/or backings that are commercially available, includingfilms (e.g., polyurethane films), hydrocolloids (e.g., hydrophiliccolloidal particles bound to polyurethane foam), hydrogels (e.g.,cross-linked polymers containing about at least 60% water), foams(hydrophilic or hydrophobic), calcium alginates (e.g. non-wovencomposites of fibers from calcium alginate), silicone, collagen,keratin, and cellophane (e.g. cellulose with a plasticizer). Thesubstrate can also be a fish skin extracellular matrix (ECM) material(i.e. scaffold material) as described in Sigurjonsson et al., U.S.patent application Ser. No. 12/899,123, filed on Oct. 6, 2010, or apolyurethane wound dressing such as the wound dressing described inSigurjonsson, U.S. Pat. No. 7,230,154.

For example, the stabilized formulation can be applied to the surfaceof, or incorporated into, a solid contacting layer such as a dressinggauze or matrix. Suitable gauze dressings may include, for example, drywoven or non-woven sponges, swabs, bandages and wraps with varyingdegrees of absorbency. Exemplary fabric composition may include, forexample, cotton, polyester or rayon. In certain embodiments, gauzes andnon-woven dressings may be available sterile or non-sterile in bulk andwith or without an adhesive border. In certain embodiments the dressingsalso comprise one or more additional pharmaceutically active compoundand/or carrier agent, including for example, saline, oil, zinc salts,petrolatum, xeroform and scarlet red.

An example composition suitable for application to a wound, including anopen wound, is a sterile liquid composition comprising the stabilizedformulation in combination with polyacrylic acid, polyacrylic acrylate,xanthan gum, guar gum, hydoxyl cellulose, and/or silicon.

In another embodiment, the omega-3 polyunsaturated fatty acids describedherein are combined with AHA in the absence of at least one of the othercomponents of the stabilized formulation (i.e. tocopherol (Vitamin E),ascorbic acid (Vitamin C), herb extract, and a fat-soluble antioxidant).In this embodiment, the composition can comprise any one or more of theadditional therapeutically active compounds and pharmaceutically and/orcosmetically acceptable diluents, excipients or carriers describedherein. A composition that does not comprise the stabilized formulationcan be formulated for topical application as described herein and sealedin an air tight container suitable for a single use. Such a compositioncan be used to treat any of the skin conditions and/or wounds describedherein, for example a skin condition and/or wound present on thediabetic foot.

The dosage regimen for treating skin conditions and/or wounds isselected in accordance with a variety of factors, including the age,weight, sex, and medical condition of the patient, the severity of thecondition, the route of administration, pharmacological considerationssuch as the activity, efficacy, pharmacokinetic and toxicology profilesof the particular composition used, whether a dressing or drug deliverysystem is used and whether the composition is administered as part of adrug combination.

The doses may be administered in single or divided applications. Thedoses may be administered once, or application may be repeated.Application may be repeated weekly until skin and/or wound healing ispromoted, or a repeat application may be made in the event that healingslows or is stalled. Doses may be applied 1-7 days apart, or more. Inthe case of a chronic skin condition or wound, repeat applications maybe made, for example, one or more times per day, weekly, or bi-weekly,or monthly or in any other frequency for example if and when healingslows or is stalled. For some indications more frequent dosing such ashourly application may be employed.

“Treatment” or “treating,” as used herein, refers to completeelimination as well as to any clinically or quantitatively measurablehealing or alleviation of the symptoms of the skin condition and/orwound. A “therapeutically effective amount” means the amount of acomposition that, when administered to a subject for treating a skincondition and/or wound, is sufficient to effect a desirable treatmentfor the skin condition and/or wound. The “therapeutically effectiveamount” will vary depending on the particular composition, the conditionand its type and severity, and the age, weight, etc., of the subject tobe treated. A “therapeutically effective amount” need not result in acomplete cure, but may provide partial relief of one or more symptoms orretard the progression of a condition such as dryness.

“Patient” or “subject” refers to animals, and can include any mammal,such as humans, rats, mice, cats, dogs, goats, sheep, horses, monkeys,apes, rabbits, cattle, etc. The mammalian subject can be in any stage ofdevelopment including adults, children, infants, and neonates.

As used herein, the singular forms “a”, “an” and “the” include pluralreferents unless the context clearly dictates otherwise.

The publications disclosed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein should be construed as an admission that the present disclosureis not entitled to antedate such publication by virtue of priordisclosure. Further, the dates of publication provided may be differentfrom the actual publication dates, which may need to be independentlyconfirmed. All publications, patents, patent applications and otherreferences cited herein are hereby incorporated by reference in theirentirety.

While the disclosure has been described in detail with reference tocertain embodiments thereof, it will be apparent to one skilled in theart that various changes can be made, and equivalents employed, withoutdeparting from the scope of the disclosure. In addition, the followingexamples are illustrative only and should not be considered as limitingthe disclosure in any way.

EXAMPLES Example 1 Stabilized Formulations (wt %)

(1)

-   -   0.05% Vit.E    -   3% Vit.C    -   0.5% Rosemary    -   0.25% BHT or BHA    -   96.2% Omega-3 Fish Oil (Lysi Ltd., Iceland)

(2)

-   -   0.25% Vit.E    -   2% Vit.C    -   0.25% Rosemary    -   0.25% BHT or BHA    -   97.25% Omega-3 Fish Oil (Lysi Ltd., Iceland)

(3)

-   -   0.1% Vit.E    -   1% Vit.C    -   0.5% Rosemary    -   0.1% BHT or BHA    -   98.3% Omega-3 Fish Oil (Lysi Ltd., Iceland)

(4)

-   -   0.05% Vit.E    -   1% Vit.C.    -   0.25% Rosemary    -   0.5% BHT or BHA    -   98.2% Omega-3 Fish. Oil (Lysi Ltd., Iceland)

Example 2 Foot Cream Formulations and Preparation Protocol

TABLE 1 Formulation I Amount Purpose Part Lanolin alcohol 27%  EmollientA Cetearyl alcohol Emulsion stabilizer Petrolatum Emollient Urea 10% Humectant C AHA 7% Peeling agent B Paraffine liquid 5% Emollient APolypropylene glycol 4% Humectant B Stabilized formulation 3% — C Sodiumacrylates copolymer 2.5%   Thickener C PPG-1 Trideceth-6 ThickenerPolydecane Thickener Steareth-100 1% Emulsifier B Steareth-2 sucroseEmulsifier Xanthan Gum Thickener Tocopherol 1% anti oxidant C methylparaben 0.1%   Preservative C ethyl paraben Preservative propyl parabenPreservative Phenoxyethanol Preservative Fragrance oil 0.01%   fragranceoil* Aqua 39.4%   Aqua B Triethanolamine if needed pH modifier *e.g.almond, vanilla, green tea, mountain rain, vetever, pinapple, grapefruit. . .

TABLE 2 Formulation II Amount Purpose Part Lanolin alcohol 27% Emollient A Cetearyl alcohol emulsion stabilizer Petrolatum EmollientUrea 10%  Humectant C AHA 7% peeling agent B Paraffine liquid 5%Emollient A Polypropylene glycol 4% Humectant B Stabilized formulation3% — C Sodium polyacrylate 2% Thickener C Mineral oil (USA/CTFA)Thickener Trideceth-6 Thickener Steareth-100 1% Emulsifier B Steareth-2sucrose Emulsifier Xanthan Gum Thickener Tocopherol 1% anti oxidant Cmethyl paraben 0.1%   Preservative C ethyl paraben Preservative propylparaben Preservative Phenoxyethanol Preservative Fragrance oil 0.01%  fragrance oil* Aqua 39.9%   Aqua B Triethanolamine if needed pH modifier*e.g. almond, vanilla, green tea, mountain rain, vetever, pinapple,grapefruit . . .

TABLE 3 Formulation III Amount Purpose Part Lanolin alcohol 27% Emollient A Cetearyl alcohol emulsion stabiliser Petrolatum EmollientUrea 10%  Humectant C AHA 7% peeling agent B Paraffine liquid 5%Emollient A Polypropylene glycol 4% Humectant B Stabilized formulation3% — C Sodium polyacrylate 2% Thickener C Mineral oil (USA/CTFA)Thickener Trideceth-6 Thickener Sucrose Palmitate 1% Emulsifier BGlyceryl Stearate Emulsifier Glyceryl Stearate Citrate Emulsifier MannanThickener Xanthan Gum Thickener Tocopherol 1% anti oxidant C methylparaben 0.1%   Preservative C ethyl paraben Preservative propyl parabenPreservative Phenoxyethanol Preservative Fragrance oil 0.01%   fragranceoil* Aqua 39.9%   Aqua B Triethanolamine if needed pH modifier *e.g.almond, vanilla, green tea, mountain rain, vetever, pinapple, grapefruit. . .

TABLE 4 Formulation IV Amount Purpose Part Lanolin alcohol 27% Emollient A Cetearyl alcohol Emulsion stabiliser Petrolatum EmollientUrea 10%  Humectant C AHA 7% Peeling agent B Paraffine liquid 5%Emollient A Polypropylene glycol 4% Humectant B Stabilized formulation3% — C Sodium acrylates copolymer 2.5%   Thickener C PPG-1 Trideceth-6Thickener Polydecane Thickener Steareth-100 1% Emulsifier B Steareth-2sucrose Emulsifier Xanthan Gum Thickener Tocopherol 1% anti oxidant Cmethyl paraben 0.1%   Preservative C ethyl paraben Preservative propylparaben Preservative Phenoxyethanol Preservative Rosemary extract0.05%   anti oxidant C Fragrance oil 0.01%   fragrance oil* Aqua 38.9%  Aqua B Triethanolamine if needed pH modifier *e.g. almond, vanilla,green tea, mountain rain, vetever, pinapple, grapefruit . . .

Preparation

1. Heat phases A and B separately up to T=70-80° C., preferrably in awater bath.

2. Phase B is put in a mixer ans phase A poured gently into the mixturewith continuos powerful stirring.

3. Continue stirring while mixture cools down to 40° C.

4. Add phase C to the mixture.

5. Continue with powerful stirring until mixture has cooled down to roomtemperature

6. Add fragrance oil

7. Measure pH and adjust with trethanolamine if necessary (preferredpH=3.0-3.5)

The first step in preparation of the cream is to make two differentsolutions; a fat based solution and an aqueous solution. The fat basedsolution is prepared by heating the oils and fat-soluble chemicals(lanolin alcohol, ceteryl alcohol, petrolatum, paraffin liquid . . . )up 70-80° C. The aqueous solution is prepared by heating the water andwater-soluble chemicals (aqua, polypropylene glycol, AHA . . . ) up tothe same temperature as the fat-based solution. When both mixtures areheated they are carefully mixed together by pouring them into a powerfulstirrer. The oils are first put into the mixer and then the aqueoussolution is poured in little by little. The mixture should be stirredthe whole time while cooling down, or it will separate. When cooled downto about 40° C., the polyunsaturated fatty acids (i.e. the stabilizedformulation) and urea are mixed together with thickening agents,antioxidants and preservatives and added to the mixture. The cream isnow kept in the mixer with continuously stirred until cooled down toroom temperature. Finally fragrance is added to the cream and the pH ismeasured and adjusted to pH of 2-5 (such as 3.0-3.5) if necessary withtriethanolamin.

The proportion of the active ingredients (polyunsaturated fatty acids,AHA and urea) can vary at least about ±2% without the cream losing itsquality. A small variation in concentration is also acceptable for thecarriers (e.g. the various thickening and emulsifying agents).

Example 3 Skin Cream Formulations

A. Stabilized formulation, purified water, liquid paraffin (mineraloil), petrolatum, alcohol, glyceryl stearate, PEG-100 stearate,paraffin, lecithin, polysorbate 60, DEA-cetyl phosphate, dimethicone,carbomer, imidazolidinyl urea, methylparaben, propylparaben,triethanolamine, fragrance.

B. Stabilized formulation, purified water, olive oil, glycerin,pentylene glycol, palm glycerides, vegetable oil, hydrogenated lecithin,squalene, betaine, palmitamide MEA, sarcosine, acetamide MEA,hydroxethyl cellulose, sodium carbomer, xanthan gum.

C. Stabilized formulation, purified water, liquid paraffin, ethyleneglycol monostearate, stearic acid, propylene glycol, paraffin wax,squalene, avocado oil, trolamine/sodium alginate, triethanolamine, cetylpalmitate, methylparaben (sodium salt), sorbic acid (potassium salt),polyparaben (sodium salt), fragrance.

Example 4 Wound Guard Formulations

A. Stabilized formulation, alpha hydroxyl acid (AHA), purified water,liquid paraffin (mineral oil), petrolatum, alcohol, glyceryl stearate,PEG-100 stearate, paraffin, lecithin, polysorbate 60, DEA-cetylphosphate, dimethicone, carbomer, imidazollidinyl urea, methylparaben,propylparaben, triethanolamine, fragrance.

B. Stabilized formulation, alpha hydroxyl acid (AHA), purified water,liquid paraffin, ethylene glycol monosterate, stearic acid, propyleneglycol, paraffin wax, squalene, avocado oil, trolamine/sodium alginate,triethanolamine, cetyl palmitate, methylparaben (sodium salt), sorbicacid (potassium salt), polyparaben (sodium salt), fragrance.

C. Stabilized formulation, alpha hydroxyl acid (AHA), purified water,olive oil, glycerin, pentylene glycol, palm glycerides, vegetable oil,hydrogenated lecithin, squalene, betaine, palmitamide MEA, sarcosine,acetamide MEA, hydroxyethyl cellulose, sodium carbomer, xanthan gum.

Example 5 Hydrocolloid Wound Dressing

Stabilized Formulation:

-   -   0.05% Vit.E    -   3% Vit.C    -   0.5% Rosemary extract    -   0.25% BHT or BHA    -   96.2% Omega-3 Fish Oil (Lysi Ltd., Iceland)

The Omega-3 component (stabilized formulation) is added to ahydrocolloid component that has been heated to become viscous. Thecomponents are then mixed together, and the Omega-3-hydrocolloid mixtureis poured onto molds and left for cooling.

Example 6 Wound Contact Layer

Stabilized Formulation:

-   -   0.1% Vit.E    -   1% Vit.C    -   0.5% Rosemary extract    -   0.1% BHT or BHA    -   98.3% Omega-3 Fish Oil (Lysi Ltd., Iceland)

The Omega-3 component (stabilized formulation) is mixed together with ahydrogel component. The Omega-3-hydrogel mixture is then applied to apolyurethane dressing as a wound contact layer (i.e. applied to the sideof the polyurethane wound dressing that will be proximal to the woundbed).

Example 7 Omega-3 Collagen Wound Dressing

Stabilized Formulation:

-   -   0.05% Vit.E    -   3% Vit.C    -   0.5% Rosemary extract    -   0.25% BHT or BHA    -   96.2% Omega-3 Fish Oil (Lysi Ltd., Iceland)

Wound Dressing Component:

A fish skin ECM (scaffold material) is created as described inSigurjonsson et al., U.S. patent application Ser. No. 12/899,123, filedon Oct. 6, 2010. The scaffold material is hydrolized until the texturebecomes like web paper. The stabilized formulation is poured into thematerial and material kneaded.

Example 8 Omega-3 Collagen Wound Dressing

A fish skin ECM (scaffold material) is created as described inSigurjonsson et al., U.S. patent application Ser. No. 12/899,123, filedon Oct. 6, 2010. The scaffold material is hydrolized until the texturebecomes like web paper. Omega-3 Fish Oil (Lysi Ltd., Iceland) is pouredinto the material so that the w/w of the components becomes 3/97 and thematerial is kneaded to mix the fish oil into the scaffold material.

Example 9 Omega-3 Keratin Wound Dressing

Stabilized Formulation:

-   -   0.1% Vit.E    -   1% Vit.C    -   0.5% Rosemary extract    -   0.1% BHT or BHA    -   98.3% Omega-3 Fish Oil (Lysi Ltd., Iceland)

A keratin matrix is created as described in Kelly et al., U.S. PatentApplication Publication No. 2009/0105456 A1. The Omega-3 component(stabilized formulation) is added to the keratin composition before thecasting step of the keratin manufacturing process in the ratios 1/99w/w.

What is claimed is:
 1. A method for treating a skin condition and/orwound, comprising: preparing a stabilized formulation that includes:0.05% to 0.25% tocopherol; 1% to 3% vitamin C; 0.25% to 0.5% of an herbextract; 0.1% to 0.5 of a fat-soluble antioxidant selected from thegroup consisting of BHT (butylated hydroxytoluene), BHA (butylatedhydroxyanisole), TBHQ (tertiary butyl hydroquinone), and combinationsthereof; and a balance of fish oil, wherein the fish oil comprisesomega-3 polyunsaturated fatty acids; and adding 1% to 5% of thestabilized formulation to one or more emollients, humectants, or anycombination thereof to yield a composition formulated for topicaladministration; and applying the composition to the skin conditionand/or the wound.
 2. The method of claim 1, further comprisingreapplying the composition to the skin condition and/or the wound. 3.The method of claim 1, further comprising: preparing a wound dressingfor application to the skin condition and/or the wound, wherein thewound dressing is prepared by adding the stabilized formulation to asolid or semi-solid substrate; and applying the wound dressing to theskin condition and/or the wound for protection, absorbance, drainage, orimprovement of cell environment.
 4. The method of claim 3, wherein thesolid or semi-solid substrate includes at least one of a film, ahydrocolloid, a hydrogel, a foam, an alginate, a silicone, collagen,keratin, cellophane, a fish skin extracellular matrix (ECM), or apolyurethane wound dressing.
 5. The method of claim 1, wherein the skincondition and/or wound is selected from the group consisting of dryskin, atopic dermatitis, allergic contact dermatitis, radiationdermatitis, first and second degree wounds, sunburns, superficialinjuries, abrasions, cuts, surgical wounds, pressure ulcers, venousstasis ulcers, ulcers caused by mixed etiologies, diabetic ulcers, donorsites, and grafts.
 6. The method of claim 1, wherein the skin conditionand/or wound is a diabetic ulcer.
 7. The method of claim 6, wherein thediabetic ulcer is a foot ulcer.
 8. The method of claim 1, wherein theomega-3 polyunsaturated fatty acids comprise one or more ofeicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
 9. Themethod of claim 1, wherein the herb extract is selected from the groupconsisting of rosemary, oregano, basil, marjoram, thyme, black pepper,caraway, cardamom, chives, colorifico, coriander, cumin, dill, garlic,ginger, laurel, nutmeg, onion, parsley, sage, savory and tarragonextracts, and combinations thereof.
 10. The method of claim 9, whereinthe herb extract is a rosemary extract.
 11. The method of claim 1,wherein the fat-soluble antioxidant is BHT.
 12. The method of claim 1,wherein the composition further comprises one or more additional activeagents and/or one or more pharmaceutically acceptable diluents,excipients and carriers.
 13. The method of claim 12, wherein thecomposition comprises one or more exfoliants, moisturizers, antiseptics,antimicrobial agents, antivirals, antifungals, antiparasitics,anti-inflammatory agents, antioxidants, drugs, proteins, peptides, orcombinations thereof.
 14. The method of claim 12, wherein thecomposition comprises alpha hydroxy acid (AHA).
 15. The method of claim14, wherein the AHA is one of glycolic acid or lactic acid.
 16. Themethod of claim 15, wherein glycolic acid is added to the composition inamount ranging from about 5% to 9%.
 17. The method of claim 14, whereinthe composition comprises AHA and urea.
 18. The method of claim 12,wherein the composition comprises polyacrylic acid.
 19. A method fortreating a skin condition and/or wound, comprising: preparing astabilized formulation that includes one or more exfoliants, fat solubleantioxidants, preservatives, or fragrance oils and a balance of fishoil, wherein the fish oil comprises omega-3 polyunsaturated fatty acids;adding 1% to 5% of the stabilized formulation to one or more emollients,humectants, or any combination thereof to yield a composition formulatedfor topical administration; and applying the composition to the skincondition and/or the wound.
 20. The method of claim 1, furthercomprising: preparing a wound dressing for application to the skincondition and/or the wound, wherein the wound dressing is prepared byadding the stabilized formulation to a solid or semi-solid substrate;and applying the wound dressing to the skin condition and/or the woundfor protection, absorbance, drainage, or improvement of cellenvironment.
 21. The method of claim 3, wherein the solid or semi-solidsubstrate includes at least one of a film, a hydrocolloid, a hydrogel, afoam, an alginate, a silicone, collagen, keratin, cellophane, a fishskin extracellular matrix (ECM), or a polyurethane wound dressing.